MALARIA: prospective comparative study of knowlesi, falciparum and vivax malaria in Sabah, Malaysia

A prospective comparative study of knowlesi, falciparum and vivax malaria in Sabah, Malaysia: high proportion with severe disease fromPlasmodium knowlesi and P. vivax but no mortality with early referral and artesunate therapy

1. Bridget E. Barber1,2, 
2. Timothy William1,3,4, 
3. Matthew J. Grigg1,2, 
4. Jayaram Menon3,4,
5. Sarah Auburn2, 
6. Jutta Marfurt2, 
7. Nicholas M. Anstey2,5, and 
8. Tsin W. Yeo2,5

+Author Affiliations

1. ¹Infectious Diseases Unit, Department of Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
2. ²Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia
3. ³Clinical Research Centre, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
4. ⁴Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia
5. ⁵Royal Darwin Hospital, Darwin, Northern Territory, Australia

1. Corresponding author: Prof Nicholas Anstey, Global Health Division, Menzies School of Health Research, PO Box 41096, Casuarina 0810, Northern Territory, Australia,Nicholas.Anstey@menzies.edu.au, +61 8 89228196

1. Alternate corresponding author: Dr Bridget Barber, Global Health Division, Menzies School of Health Research, PO Box 41096, Casuarina 0810, Northern Territory, Australia, bridget.barber@menzies.edu.au, +61 424737153

Abstract

Background. Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk and spectrum of severe disease from P.knowlesi, P.falciparum andP.vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria.

Methods. From September 2010-October 2011 we prospectively assessed non-pregnant patients ≥12 years-old admitted to Queen Elizabeth Hospital (QEH), Sabah, with PCR-confirmed Plasmodiummonoinfection. Standardized referral (4+ parasite-density and/or any severity-criterion) and pre-referral intravenous artesunate were instituted at district hospitals.

Results. Severe malaria (modified-WHO 2010 criteria) occurred in 38/130 (29%) patients with P.knowlesi, 13/122 (11%) with P.falciparumand 7/43 (16%) with P.vivax. Most common severity criteria in knowlesi malaria included parasitemia>100,000/µL (n=18), jaundice (n=20), respiratory distress (n=14), hypotension (n=13), and acute kidney injury (n=9). On multivariate analysis, P. knowlesi was associated with a 2.96 (95%CI:1.19-7.38)-fold greater risk of severity than P. falciparum(p=0.020); only parasitemia and schizontemia >10%, but not age, independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20,000/µL, and 28-fold with parasitemia >100,000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin-therapy; 36/38 (95%) and 39/92 (42%) with severe and non-severe disease also received ≥1 dose of intravenous artesunate. For all species, median parasite clearance-time was two days and no deaths occurred.

Conclusions. P.knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk-factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.

http://cid.oxfordjournals.org/content/early/2012/10/18/cid.cis902.abstract